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A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells.

Colonna M, Navarro F, Bellón T, Llano M, García P, Samaridis J, Angman L, Cella M, López-Botet M - J. Exp. Med. (1997)

Bottom Line: In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells.In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules.These results suggest that diverse leukocyte lineages have adopted recognition of self-MHC class I molecules as a common strategy to control cellular activation during an immune response.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Immunology, Basel CH-4005, Switzerland.

ABSTRACT
Natural killer (NK) cell-mediated lysis is negatively regulated by killer cell inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules. In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells. This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)-DR, respectively. In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules. These results suggest that diverse leukocyte lineages have adopted recognition of self-MHC class I molecules as a common strategy to control cellular activation during an immune response.

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Related in: MedlinePlus

ILT2 is associated  with SHP-1. NKL cells and the  EBV-transformed B cell line  C1R were incubated for 10 min  at 37°C either with medium alone  or with pervanadate. ILT2 was  then immunoprecipitated with  the HP-F1 mAb and immunoprecipitates were separated by  SDS-PAGE and immunoblotted  with anti–SHP-1 antibody. Whole  cell lysate is included as a positive  control. SHP-1 was recruited to  ILT2 after cell stimulation with  pervanadate.
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Figure 6: ILT2 is associated with SHP-1. NKL cells and the EBV-transformed B cell line C1R were incubated for 10 min at 37°C either with medium alone or with pervanadate. ILT2 was then immunoprecipitated with the HP-F1 mAb and immunoprecipitates were separated by SDS-PAGE and immunoblotted with anti–SHP-1 antibody. Whole cell lysate is included as a positive control. SHP-1 was recruited to ILT2 after cell stimulation with pervanadate.

Mentions: It has been shown that negative signaling through KIRs is mediated by recruitment of SHP phosphatases upon tyrosine phosphorylation of cytoplasmic ITIMs (29–33), whereas it does not involve association of SHIP phosphatase (35). The cytoplasmic tail of ILT2 contains four tyrosine-based motifs similar to those found in KIR, although only one of them fits the V/I-x-Y-x-x-L motif that has been proposed to be required for SHP-1 binding (36). To determine whether ILT2 recruits SHP phosphatases, ILT2 was immunoprecipitated from NKL cells and from the B cell line C1R either unstimulated or stimulated with pervanadate, which has been shown to induce substantial tyrosine phosphorylation of cellular substrates (37). Immunoprecipitates were immunoblotted with anti–SHP-1, anti–SHP-2 and anti-SHIP antibodies. As shown in Fig. 6, ILT2 was associated with SHP-1 after treatment with pervanadate, whereas no association was detected with SHP-2 and SHIP (data not shown).


A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells.

Colonna M, Navarro F, Bellón T, Llano M, García P, Samaridis J, Angman L, Cella M, López-Botet M - J. Exp. Med. (1997)

ILT2 is associated  with SHP-1. NKL cells and the  EBV-transformed B cell line  C1R were incubated for 10 min  at 37°C either with medium alone  or with pervanadate. ILT2 was  then immunoprecipitated with  the HP-F1 mAb and immunoprecipitates were separated by  SDS-PAGE and immunoblotted  with anti–SHP-1 antibody. Whole  cell lysate is included as a positive  control. SHP-1 was recruited to  ILT2 after cell stimulation with  pervanadate.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199153&req=5

Figure 6: ILT2 is associated with SHP-1. NKL cells and the EBV-transformed B cell line C1R were incubated for 10 min at 37°C either with medium alone or with pervanadate. ILT2 was then immunoprecipitated with the HP-F1 mAb and immunoprecipitates were separated by SDS-PAGE and immunoblotted with anti–SHP-1 antibody. Whole cell lysate is included as a positive control. SHP-1 was recruited to ILT2 after cell stimulation with pervanadate.
Mentions: It has been shown that negative signaling through KIRs is mediated by recruitment of SHP phosphatases upon tyrosine phosphorylation of cytoplasmic ITIMs (29–33), whereas it does not involve association of SHIP phosphatase (35). The cytoplasmic tail of ILT2 contains four tyrosine-based motifs similar to those found in KIR, although only one of them fits the V/I-x-Y-x-x-L motif that has been proposed to be required for SHP-1 binding (36). To determine whether ILT2 recruits SHP phosphatases, ILT2 was immunoprecipitated from NKL cells and from the B cell line C1R either unstimulated or stimulated with pervanadate, which has been shown to induce substantial tyrosine phosphorylation of cellular substrates (37). Immunoprecipitates were immunoblotted with anti–SHP-1, anti–SHP-2 and anti-SHIP antibodies. As shown in Fig. 6, ILT2 was associated with SHP-1 after treatment with pervanadate, whereas no association was detected with SHP-2 and SHIP (data not shown).

Bottom Line: In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells.In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules.These results suggest that diverse leukocyte lineages have adopted recognition of self-MHC class I molecules as a common strategy to control cellular activation during an immune response.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Immunology, Basel CH-4005, Switzerland.

ABSTRACT
Natural killer (NK) cell-mediated lysis is negatively regulated by killer cell inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules. In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells. This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)-DR, respectively. In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules. These results suggest that diverse leukocyte lineages have adopted recognition of self-MHC class I molecules as a common strategy to control cellular activation during an immune response.

Show MeSH
Related in: MedlinePlus